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1.
Anticancer Res ; 40(1): 335-339, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892584

RESUMO

BACKGROUND/AIM: The novel taxane cabazitaxel has been shown to exert excellent anticancer effects after androgen receptor axis-targeting (ARAT) agents in clinical data, but not in in vitro data. We investigated the clinical outcome of cabazitaxel chemotherapy after docetaxel according to use of ARAT agents. PATIENTS AND METHODS: Prostate specific antigen (PSA) response, progression-free survival, and overall survival were compared between cases with and without prior use of ARAT agents in 74 Japanese patients with metastatic castration-resistant prostate cancer treated with cabazitaxel chemotherapy. RESULTS: Background characteristics were comparable between patients with and without prior use of ARAT agents. PSA response, progression-free survival, and overall survival in cabazitaxel chemotherapy were comparable between patients with and without prior use of ARAT agents. CONCLUSION: No detrimental effects of prior ARAT agents on clinical outcome were observed for cabazitaxel chemotherapy in the post-docetaxel setting, suggesting that cabazitaxel can be expected to remain active even after ARAT agent therapy.


Assuntos
Antagonistas de Receptores de Andrógenos/farmacologia , Docetaxel/farmacologia , Terapia de Alvo Molecular , Receptores Androgênicos/metabolismo , Taxoides/farmacologia , Idoso , Antagonistas de Receptores de Andrógenos/uso terapêutico , Docetaxel/uso terapêutico , Humanos , Masculino , Prognóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Resultado do Tratamento
2.
Medicine (Baltimore) ; 98(52): e18513, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876741

RESUMO

BACKGROUND: This study evaluated the efficacy and safety of docetaxel combined with lobaplatin, relative to docetaxel combined with gemcitabine, for treating patients with recurrent metastatic breast cancer (rMBC). METHODS: Patients with rMBC received ≥2 cycles (21 days each) of either docetaxel and lobaplatin (DL; n = 21), or docetaxel and gemcitabine (DG; n = 22). On day 1 of each cycle, all patients were given 75 mg/m intravenous docetaxel. Patients in DL and DG were also given, respectively, 35 mg/m intravenous lobaplatin (day 2) or 1000 mg/m intravenous gemcitabine (days 1, 8). RESULTS: Five (11.6%) and 16 (37.2%) patients achieved complete remission and partial response, respectively; rates of response and disease control were 48.8%. The response rates of the groups were comparable (47.6%, 50.0%). The median survival times after relapse and metastasis of the DL group (18 months) were significantly less than that of the DG group (25 months). Median progression-free survivals after relapse and metastasis were similar (12 cf. 14 months). The main toxic side reaction was grade 2, with no treatment-related deaths. Rates of the following were comparable between DG and DL: grade 3 or 4 white blood cells (23.8%, 31.8%) and digestive tract toxicity (4.8%, 4.5%); neutropenia (28.6%, 22.7%); anemia (4.8%, nil); and thrombocytopenia (19.0%, 13.6%). Other toxicities included hepatic toxicity, myalgia, infection, and fatigue. CONCLUSIONS: Both the DL and DG regimens were associated with encouraging benefits, while treatment-related toxicity was manageable. Therefore, these regimens are effective options for treatment of rMBC. TRIAL REGISTRATION: This clinical trial study was approved by the Ethics Committee of Guizhou Cancer Hospital, and has been registered in the China Clinical Trial Center (December 8, 2014, No. ChiCTR-IPR-14005633).


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclobutanos/uso terapêutico , Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Ciclobutanos/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Docetaxel/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Projetos Piloto , Análise de Sobrevida
3.
Gan To Kagaku Ryoho ; 46(11): 1721-1725, 2019 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-31748481

RESUMO

Febrile neutropenia(FN)occurs in 3-25% of patients with castration-resistant prostate cancer(CRPC)receiving docetaxel( DTX). Therefore, the need for granulocyte colony-stimulating factor with DTX as prophylaxis has not been established. Herein, we report the efficacy of primary prophylaxis with pegfilgrastim after DTX in patients with CRPC. The subjects were 30 CRPC patients who received DTX at our hospital between January 2013 and October 2017. Twelve patients underwent primary prophylaxis with pegfilgrastim(Peg-G group), whereas the other 18 did not(control group). FN developed in 1(8.3%) and 8(44.4%)patients in the Peg-G and control groups, respectively(p=0.049). No significant differences were observed in RDI between the 2 groups. The average medical cost per course of DTX was lower in the Peg-G group than in the control group. These results demonstrate that primary prophylaxis with pegfilgrastim is useful because DTX induces FN at a high frequency in patients with CRPC, and pegfilgrastim significantly reduces its incidence without increasing the medical cost.


Assuntos
Filgrastim/uso terapêutico , Polietilenoglicóis/uso terapêutico , Neoplasias de Próstata Resistentes à Castração , Protocolos de Quimioterapia Combinada Antineoplásica , Docetaxel/uso terapêutico , Fator Estimulador de Colônias de Granulócitos , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Proteínas Recombinantes
4.
Anticancer Res ; 39(10): 5353-5359, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570429

RESUMO

BACKGROUND: Identification of genetic prognostic biomarkers, such as germline variants, are urgently needed to choose optimal treatment for metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: The prognostic value of anoctamin 7 (ANO7) rs77559646 on docetaxel response was tested in a prospective PROSTY randomized trial and a retrospective Auria Biobank set. The variant rs77559646 was genotyped and its association with progression-free survival (PFS) and overall survival (OS) was tested. RESULTS: In comparison with the non-carriers, the variant carriers had longer PFS (p=0.005) and OS (p=0.003) in the PROSTY cohort. In the retrospective cohort, there was a borderline association with PFS (p=0.09), but not in OS (p=0.9). In both cohorts, Cox regression multivariate models revealed that rs77559646 was an independent prognostic factor for favourable PFS. CONCLUSION: The rs77559646 was shown to be a prognostic germline biomarker for better response to docetaxel treatments. To our knowledge, this is the first time that a non-coding germline variant has been associated with chemotherapy of mCRPC.


Assuntos
Anoctaminas/genética , Antineoplásicos/uso terapêutico , Docetaxel/uso terapêutico , Variação Genética/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Idoso , Biomarcadores Tumorais/genética , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos
5.
Anticancer Res ; 39(10): 5803-5809, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570485

RESUMO

BACKGROUND/AIM: Cabazitaxel (CBZ) is approved for docetaxel-resistant castration-resistant prostate cancer (CRPC). This retrospective study aimed at assessing the efficacy and prognostic markers of cabazitaxel treatment in Japanese CRPC patients. PATIENTS AND METHODS: The medical records of 44 consecutive Japanese patients with CRPC who started cabazitaxel at our Institution between January 2011 and February 2019 were reviewed and statistically analysed. RESULTS: The median follow-up period after cabazitaxel initiation was 13.2 [interquartile range (IQR)=6.9-21.5] months. The objective response rate, median progression-free survival period, and median overall survival period (OS) were 45.5%, 4.3 months, and 20.7 months, respectively. On multivariate analysis, higher prostate-specific antigen (PSA; >100 ng/ml), lower haemoglobin (<10 g/dl), and lower number of prior docetaxel therapy cycles (<10) were predictors for shorter OS. CONCLUSION: Patients with anemia, high PSA, and lower number of docetaxel therapy cycles might have shorter survival period from introduction of cabazitaxel therapy. In addition, PSA decline might still be a useful indicator as a predictor of prognosis of the metastatic CRPC patients treated with cabazitaxel.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Docetaxel/uso terapêutico , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/mortalidade , Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
6.
Medicine (Baltimore) ; 98(38): e17262, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31568001

RESUMO

BACKGROUND: This study will systematically investigate the efficacy and safety of the combination of pertuzumab, trastuzumab, and docetaxel (PTD) for treatment of patients with HER2-positive breast cancer (HER2-PBC). METHODS: A comprehensive literature search for this study will consist of 2 parts: electronic database records and gray literature. The electronic database literatures are searched from PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All databases will be searched from inception up to the present. In addition, gray literatures, such as dissertations, ongoing trials, and so on, will also be searched. Two authors will independently read the records, extract data collection, and evaluate the risk of bias. RevMan V.5.3 software will be applied for statistical analysis. RESULTS: This study will summarize up-to-date evidence of PTD for patients with HER2-PBC via overall survival, complete response, cancer-specific survival, recurrence-free survival, disease-free survival, quality of life, and toxicities. CONCLUSION: This study will provide efficacy and safety of PTD for HER2-PBC.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Docetaxel/uso terapêutico , Genes erbB-2 , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Docetaxel/administração & dosagem , Feminino , Humanos , Trastuzumab/administração & dosagem , Resultado do Tratamento
7.
Genes (Basel) ; 10(8)2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398933

RESUMO

Prostate cancer is the fifth leading cause of male cancer death worldwide. Although docetaxel chemotherapy has been used for more than fifteen years to treat metastatic castration resistant prostate cancer, the high inter-individual variability of treatment efficacy and toxicity is still not well understood. Since prostate cancer has a high heritability, inherited biomarkers of the genomic signature may be appropriate tools to guide treatment. In this review, we provide an extensive overview and discuss the current state of the art of pharmacogenomic biomarkers modulating docetaxel treatment of prostate cancer. This includes (1) research studies with a focus on germline genomic biomarkers, (2) clinical trials including a range of genetic signatures, and (3) their implementation in treatment guidelines. Based on this work, we suggest that one of the most promising approaches to improve clinical predictive capacity of pharmacogenomic biomarkers in docetaxel treatment of prostate cancer is the use of compound, multigene pharmacogenomic panels defined by specific clinical outcome measures. In conclusion, we discuss the challenges of integrating prostate cancer pharmacogenomic biomarkers into the clinic and the strategies that can be employed to allow a more comprehensive, evidence-based approach to facilitate their clinical integration. Expanding the integration of pharmacogenetic markers in prostate cancer treatment procedures will enhance precision medicine and ultimately improve patient outcomes.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Docetaxel/uso terapêutico , Variantes Farmacogenômicos , Neoplasias de Próstata Resistentes à Castração/genética , Animais , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico
8.
BMC Cancer ; 19(1): 766, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382926

RESUMO

BACKGROUND: To describe the patterns of second-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel treatment in a Spanish population, to identify the factors associated with those patterns, and to compare the efficacy and safety of the treatments most frequently administered. METHODS: Observational, prospective study conducted in patients with histologically or cytologically confirmed prostate adenocarcinoma; documented metastatic castration-resistant disease; progression after first-line, docetaxel-based chemotherapy with or without other agents. RESULTS: Of the 150 patients recruited into the study, 100 patients were prescribed abiraterone acetate plus prednisone (AAP), 44 patients received cabazitaxel plus prednisone (CP), and 6 patients received other treatments. Age (odds ratio [OR] 1.06, 95% [confidence interval] CI 1.01 to 1.11) and not elevated lactate dehydrogenase (LDH) levels (OR 0.33, 95% CI 0.14 to 0.76) were independently associated with the administration of AAP. Treatment with AAP was associated with significantly longer clinical/radiographic progression-free survival (hazard ratio [HR] 0.57, 95% CI 0.38 to 0.85) and overall survival (OS; HR 0.40, 95% CI 0.21 to 0.76) compared to CP, while no significant differences between the treatments were found regarding biochemical progression-free survival (PFS; HR 0.78 [95% CI 0.49 to 1.24]). However, in a post-hoc Cox regression analysis adjusted for potential confounders there were not differences between AAP and CP in any of the time-to-event outcomes, including overall survival. We observed no new safety signals related to either regimen. CONCLUSION: Second-line AAP for patients with mCRPC is the most common treatment strategy after progression with a docetaxel-based regimen. When controlling for potential confounders, patients receiving this treatment showed no differences in PFS and OS in comparison to those receiving CP, although these latter results should be confirmed in randomized controlled trials.


Assuntos
Acetato de Abiraterona/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Docetaxel/uso terapêutico , Prednisona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Acetato de Abiraterona/efeitos adversos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia/etiologia , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Astenia/etiologia , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/análise , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Dor/etiologia , Prednisona/efeitos adversos , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Espanha , Taxoides/efeitos adversos , Resultado do Tratamento
9.
Crit Rev Oncol Hematol ; 142: 16-25, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31326706

RESUMO

BACKGROUND: Two PD-1 (pembrolizumab, nivolumab) and one PD-L1(atezolizumab) inhibitors are approved for previously treated advanced non-small cell lung cancer but have not been compared in head-to-head trials. METHOD: A network meta-analysis was conducted to compare efficacy/safety of PD-1/PD-L1 inhibitors. RESULTS: In five-trials (including long-term updates) with docetaxel as common comparator there were no differences in OS and PFS between PD-1/PD-L1 inhibitors. Pembrolizumab (odds ratio(OR) = 2.22, 95%CrI = 1.28-3.70) and nivolumab (OR = 1.92, 95%CrI = 1.15-3.23) had higher ORRs than atezolizumab and at PD-L1 expression ≥50% and ≥1%. Probabilistically, pembrolizumab ranked first in OS and ORR, and in OS sub-analyses for adenocarcinoma, EGFR-mutant, ECOG-score-1, male, and age <65 years. Nivolumab ranked first in PFS, and in OS sub-analyses for squamous-cell disease, EGFR-wild-type, and ECOG-score-0. Pembrolizumab and nivolumab ranked the best option for most of adverse events. CONCLUSION: While pembrolizumab and nivolumab prevailed in rank in OS and ORR benefit, patient characteristics, safety and tolerance should be considered in treatment decision-making.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Meta-Análise em Rede , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Docetaxel/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do Tratamento
10.
BMC Cancer ; 19(1): 720, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331293

RESUMO

BACKGROUND: Interstitial pneumonitis is a rare reaction in a previously irradiated area of pulmonary or thoracic lesion after treatment with anticancer drugs such as taxanes. CASE PRESENTATION: A 66-year-old man presented with a fever and dyspnea after treatment with cabazitaxel for castration-resistant prostate cancer. He was treated with an intravenous broad-spectrum antimicrobial agent, however he complained of dyspnea and had a pulse oximetric saturation of 80% while breathing room air. The patients had been treated for bone metastases with 37.5 Gy to the thoracic spine (Th 7) as a local radiotherapy. Radiological images showed pulmonary interstitial opacities in the irradiated field of the both lungs. The steroid pulse therapy was started. The patient's dyspnea disappeared and the interstitial opacities had also improved. CONCLUSIONS: This report is a case of interstitial pneumonitis in a castration-resistant prostate cancer patient receiving cabazitaxel after thoracic radiation therapy.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Doenças Pulmonares Intersticiais/induzido quimicamente , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Administração Intravenosa , Idoso , Antineoplásicos/administração & dosagem , Docetaxel/efeitos adversos , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Dispneia/tratamento farmacológico , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Taxoides/administração & dosagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Future Oncol ; 15(23): 2699-2706, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31282758

RESUMO

Aim: To assess outcomes in patients with advanced adenocarcinoma non-small-cell lung cancer who received nintedanib plus docetaxel after progression on prior chemotherapy followed by immune checkpoint inhibitor (ICI) therapy. Patients & methods: VARGADO is a prospective, noninterventional study. We describe initial data from a cohort of 22 patients who received nintedanib plus docetaxel after chemotherapy and ICI therapy. Results: Median progression-free survival with nintedanib plus docetaxel was 5.5 months (95% CI: 1.9-8.7 months). The objective response rate was 7/12 (58%) and the disease control rate was 10/12 (83%). Data for overall survival rate 12 months after the start of treatment (primary end point) are not yet mature and are not reported. Of 22 patients, 73% experienced drug-related adverse events; adverse events led to treatment discontinuation in 32% of patients. Conclusion: These data highlight the potential clinical benefit of nintedanib plus docetaxel in patients who failed prior ICI therapy. Trial registration number: NCT02392455.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/uso terapêutico , Indóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Docetaxel/efeitos adversos , Feminino , Humanos , Indóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
12.
Medicine (Baltimore) ; 98(26): e16065, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261514

RESUMO

BACKGROUND: Apatinib is an oral small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Some clinical trials have demonstrated that apatinib is efficacious against advanced nonsquamous NSCLC. OBJECTIVE: This study aimed to probe efficacy and safety of apatinib plus docetaxel, as the second or above line treatment, in advanced nonsquamous NSCLC. DESIGN: Multicenter, prospective, single arm study. SETTING: Three teaching hospitals centers in the Sichuan. PARTICIPANTS: Fourteen patients with stage IVA/B nonsquamous NSCLC had previously received at least 1 platinum-based chemotherapy regimen. INTERVENTION: Patients who were enrolled between November 2016 and January 2018 were given docetaxel (75 mg/m, i.v., d1) plus oral apatinib (250 mg/d), 4 weeks as one cycle, until disease progression or intolerance to adverse events (AE). MAIN OUTCOME MEASURES: The primary endpoint was progression-free survival (PFS). The secondary endpoints comprised objective response rate (ORR), disease control rate (DCR), overall survival (OS), and AE incidence rate. RESULTS: All patients carried adenocarcinoma by pathological type. The median follow-up duration was 9.76 months. Out of 14 cases, 12 were evaluable, showing ORR of 33.33%, DCR of 66.67%, DCR of 50% in cases with brain metastasis, median PFS of 2.92 months (95% CI: 1.38-4.48), and 6-month OS of 80%. Primary AEs encompassed: leukopenia in 7 cases (58.33%), hand-foot skin reaction in 5 cases (41.67%), and diarrhea in 4 cases (33.33%). Among them, grade 3 AEs were: leukopenia in 4 cases (33.33%), and hand-foot skin reaction in 1 case (8.33%). No grade 4/5 AEs were reported. Univariate and multivariate analysis were conducted respectively for PFS and OS. These factors encompassed: gender, age, gene mutations, clinical stage, ECOG scores, quantity of metastatic foci, brain metastasis, and hand-foot skin reaction. Results demonstrated zero risk factors for PFS or OS. CONCLUSION: Apatinib plus docetaxel, as the second or above line treatment, is effective and safe against advanced nonsquamous NSCLC, with good tolerance profile. TRIAL REGISTRATION: NCT03416231.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Piridinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Progressão da Doença , Docetaxel/efeitos adversos , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Dados Preliminares , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/efeitos adversos , Retratamento , Análise de Sobrevida , Resultado do Tratamento , Moduladores de Tubulina/efeitos adversos , Moduladores de Tubulina/uso terapêutico
13.
Anticancer Res ; 39(7): 3879-3885, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262916

RESUMO

BACKGROUND/AIM: There are few reports that verify the relationship between the therapeutic effects of flutamide and novel androgen receptor-targeted agents. We aimed to evaluate the benefits of flutamide as an alternative anti-androgen agent and its effects on the efficacy of novel androgen receptor-targeted agents. PATIENTS AND METHODS: Patients with castration-resistant prostate cancer on novel androgen receptor-targeted agents without prior docetaxel therapy were included. Changes in prostate-specific antigen (PSA) level were recorded. RESULTS: Patients who responded well to flutamide (Flutamide effective) following initial maximum androgen blockade (MAB) showed significantly higher changes in serum PSA levels (p=0.039) and PSA-progression-free survival (PFS) rate (p=0.016) following enzalutamide therapy compared to those who did not respond well to flutamide. Multivariate analysis showed that the factor of Flutamide effective was significantly associated with a good PSA-PFS rate following enzalutamide therapy (HR=7.36, 95%CI=1.4-38.71, p=0.018). CONCLUSION: Patients showing good response to flutamide following initial MAB may achieve a satisfactory PSA-PFS rate with subsequent enzalutamide therapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Flutamida/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acetato de Abiraterona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Feniltioidantoína/análogos & derivados , Feniltioidantoína/uso terapêutico , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Receptores Androgênicos , Resultado do Tratamento
14.
Anticancer Res ; 39(7): 3901-3908, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262919

RESUMO

BACKGROUND/AIM: Abiraterone (AA) and enzalutamide (ENZ) were introduced in Taiwan since 2012 for the treatment of patients with post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). This study aims to retrospectively compare the efficacy of the two regimens. MATERIALS AND METHODS: The study cohort consisted of 77 mCRPC patients previously treated with docetaxel and subsequently with AA (n=63, the AA group) or ENZ (n=13, the ENZ group), all treated in our hospital. Clinical parameters of the two groups were compared to determine differences between pre-treatment variables and treatment outcomes. RESULTS: Sixty-four patients received AA and 13 received ENZ, with a median 18.2 vs. 14.5 months follow-up (p=0.434). Prostate-specific antigen (PSA) response >50% was 31 (48.4%) in AA and 9 (69.2%) in ENZ (p=0.171), while PSA response >90% was 16 (25%) in AA and 5 (38.5%) in ENZ (p=0.32). The median progression-free survival (PFS) was 7.3 (95%CI=4.796-9.804) months in AA and 9.5 months (95%CI=5.743-13.257) in ENZ (p of log rank=0.766). The median overall survival (OS) from second-line hormone treatment was 30.2 months in AA group and 16.2 months in ENZ group (p of log rank=0.734). Neither the uni- nor the multi-variate COX-regression analysis distinguished any advantage of the two-drug regimen in terms of PFS or OS. Metastasis volume (HR=3.032, 95%CI=1.281-7.178, p=0.012) and nadir PSA (HR=1.000, 95%CI=1.000-1.001, p=0.010) were shown as independent risk factors for the survival of AA/ENZ-treated patients. CONCLUSION: AA and ENZ had a similar efficacy in treating post-docetaxel mCRPC patients. Metastatic volume and nadir PSA were independent risk factors of these patients in predicting their disease-specific survival and overall survival.


Assuntos
Acetato de Abiraterona/uso terapêutico , Antineoplásicos/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Docetaxel/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/patologia , Resultado do Tratamento
15.
Pharm Dev Technol ; 24(9): 1164-1174, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31340709

RESUMO

We prepared octreotide (OCT)-modified curcumin plus docetaxel micelles to enhance active targeting and inhibit tumor metastasis by destroying vasculogenic mimicry (VM) channels. Soluplus was applied as an amphiphilic material to form micelles via film dispersion. The cytotoxic effects, active cellular targeting, and inhibitory effects on metastasis were systematically evaluated in vitro using A549 cells, and in vivo antitumor effects were evaluated using xenograft tumor-bearing mice. In vitro assays indicated that the OCT-modified curcumin plus docetaxel micelles showed robust cytotoxicity on A549 cells and effectively inhibited VM channels and tumor metastasis. Studying the mechanism of action indicated that OCT-modified curcumin plus docetaxel micelles downregulated MMP-2 and HIF-1α. In vivo assays indicated that OCT-modified curcumin plus docetaxel micelles increased drug accumulation at tumor sites and showed obvious antitumor efficacy. The developed OCT-modified curcumin plus docetaxel micelles may offer a promising treatment strategy for non-small-cell lung cancer.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Curcumina/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Octreotida/administração & dosagem , Células A549 , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Curcumina/análogos & derivados , Curcumina/farmacocinética , Curcumina/uso terapêutico , Docetaxel/farmacocinética , Docetaxel/uso terapêutico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Octreotida/análogos & derivados , Octreotida/farmacocinética , Octreotida/uso terapêutico , Polietilenoglicóis/química , Polivinil/química
16.
BMC Cancer ; 19(1): 524, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151428

RESUMO

BACKGROUND: Abiraterone is an important agent in the treatment of advanced prostate cancer. Early changes in prostate-specific antigen while on abiraterone in patients with metastatic castrate-resistant prostate cancer potentially have financial and health implications for patients. Limited data is available on early prostate-specific antigen change and subsequent survival given phase III trials did not measure prostate-specific antigen changes before 12 weeks. METHODS: A single-center retrospective study was performed. Metastatic castrate-resistant prostate cancer patients treated with abiraterone (without prior enzalutamide) at Tulane Cancer Center were reviewed with a focus on early prostate-specific antigen decline and relationship to overall survival. RESULTS: A total of 110 patients were analyzed for prostate-specific antigen response of ≥ 30 and > 50% at 4, 8, and 12 weeks. A prostate-specific antigen response of either > 30% or > 50% at 4, 8, or 12 weeks was associated with improved overall survival at all time points except > 50% decline at 8 weeks. Multivariate analysis indicated, for all time points, that early prostate-specific antigen declines were predictive of overall survival. The neutrophil to lymphocyte ratio and docetaxel pretreatment also were predictive in many, but not all, of the multivariate analyses. CONCLUSIONS: A > 30% or > 50% prostate-specific antigen decline at 4, 8, or 12 weeks provides important information regarding subsequent overall survival for patients with metastatic castrate-resistant prostate cancer. While these data require validation with a large, multi-institutional trial, they can provide physicians with information regarding prognosis and the timing of expected outcomes. These data affirms the notion that prostate-specific antigen responses as early as 4 weeks after abiraterone initiation can be used to inform both patients and physicians about metastatic castrate-resistant prostate cancer outcomes after initiating treatment with this important but costly therapeutic choice.


Assuntos
Androstenos/uso terapêutico , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Docetaxel/uso terapêutico , Humanos , Contagem de Leucócitos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Prognóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/secundário , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
17.
Oncol Res Treat ; 42(7-8): 366-374, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31170721

RESUMO

BACKGROUND: To provide rapid evaluation of patients with advanced urological malignancies, a joint urological-oncological clinic was initiated at our institution in January 2015. We present the first 3-year evaluation of this joint urological-oncological clinic in Switzerland. METHOD: We performed a retrospective analysis of the characteristics and treatment of all patients reviewed at the joint clinic between January 2015 and December 2017. Statistical analysis was performed by survival analysis. A patient satisfaction questionnaire was handed out to new patients (from April to September 2017). RESULTS: A total of 135 new patients were counseled in the joint clinic and 563 consultations were performed in the period from January 2015 to December 2017. The majority were men with prostate cancer (85%), followed by bladder cancer (9%), and renal cell carcinoma (4%). Men with newly diagnosed metastatic prostate cancer (n = 69) received ADT alone (57%), ADT with docetaxel or abiraterone (33%), and metastasis-directed therapy (10%). High rates of patient satisfaction were reported based on the questionnaire. CONCLUSIONS: The joint clinic model has been successfully implemented at our institution and continues on a weekly basis. The clinic is increasingly used, not only for newly diagnosed metastatic prostate cancer, but also for other complex uro-oncological cases. The clinic allows optimized oncological treatment without delay and with a reduced effort for patients.


Assuntos
Relações Interprofissionais , Neoplasias Urológicas/classificação , Neoplasias Urológicas/tratamento farmacológico , Acetato de Abiraterona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Docetaxel/uso terapêutico , Humanos , Masculino , Oncologia , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Análise de Sobrevida , Suíça , Resultado do Tratamento , Urologia
18.
BMC Cancer ; 19(1): 562, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185946

RESUMO

BACKGROUND: Cabazitaxel (CBZ) chemotherapy for metastatic castration-resistant prostate cancer (mCRPC) is believed to be palliative because the radiological response rate is low and a durable response is rare. Here, we describe a rare case of a patient with mCRPC who was treated with CBZ chemotherapy and showed a durable radiological response and a complete biochemical response. CASE PRESENTATION: A 43-year-old man with prostate cancer and metastasis of the pubic bone underwent neoadjuvant androgen deprivation and docetaxel therapy, followed by laparoscopic prostatectomy, extended lymphadenectomy, and metastatectomy in 2014. Pathological examination revealed residual adenocarcinoma in the prostate and pubic bone (pathological T stage 3b, positive surgical margin). Following the operation, he received adjuvant radiation therapy (66 Gy) to the pelvic floor. His serum prostate-specific antigen (PSA) level decreased to < 0.01 ng/mL but gradually increased following docetaxel chemotherapy. Imaging findings indicated five tiny nodules in the bilateral lungs. Biopsy specimens are difficult to obtain and might not reflect the precise extent of the disease owing to heterogeneity in patients with CRPC. Thus, we performed liquid biopsy to isolate circulating tumor cells (CTCs), and overall 156 CTCs were detected per 7.5 mL. Almost all CTCs were androgen receptor-negative in the nucleus. We diagnosed the five nodules as lung metastases from docetaxel-resistant CRPC with few AR-signaling-dependent cancer cells. The patient was initiated on CBZ chemotherapy (25 mg/m2) according to the standard protocol in August 2016, instead of using a second-generation AR-targeting agent. After 2 cycles of CBZ chemotherapy, PSA level decreased to < 0.01 ng/mL and the lung metastases completely disappeared, with a reduced CTC count of < 5. To date, the patient has been receiving intermittent CBZ chemotherapy. CONCLUSIONS: We presented a rare case of a patient with mCRPC who was successfully treated with early CBZ chemotherapy. The early detection of metastasis using liquid biopsy enabled the introduction of early CBZ chemotherapy for docetaxel-resistant mCRPC.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/secundário , Antineoplásicos/uso terapêutico , Detecção Precoce de Câncer , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/uso terapêutico , Adenocarcinoma de Pulmão/diagnóstico , Adulto , Antineoplásicos/administração & dosagem , Docetaxel/efeitos adversos , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Biópsia Líquida , Neoplasias Pulmonares/diagnóstico , Masculino , Células Neoplásicas Circulantes , Antígeno Prostático Específico/sangue , Receptores Androgênicos/metabolismo , Taxoides/administração & dosagem , Resultado do Tratamento
19.
Medicina (Kaunas) ; 55(6)2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31226865

RESUMO

Background and Oobjectives: Lung cancer, a pressing issue in present-day society due to its high prevalence and mortality rate, can be managed effectively by long-term delivery of anticancer agents encapsulated in nanoparticles in the form of inhalable dry powder. This approach is expected to be of strategic importance in the management of lung cancer and is a developing area in current research. In the present investigation, we report on the formulation and characterization of docetaxel inhalable nanoparticles as a viable alternative for effective treatment of non-small cell lung cancer as a long-term delivery choice. Materials and Methods: Poloxamer (PLX-188) coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing docetaxel (DTX-NPs) were prepared by simple oil in water (o/w) single emulsification-solvent evaporation process. The nanoparticles were collected as pellet by centrifugation, dispersed in mannitol solution, and lyophilized to get dry powder. Results: Optimized DTX-NPs were smooth and spherical in morphology, had particle size around 200 nm, zeta potential around -36 mV, and entrapment efficiency of around 60%. The invitro anticancer assay was assessed and it was observed that nanoparticle-based formulation exhibited enhanced cytotoxicity when compared to the free form of the drug post 48 h. On examining for invitro drug release, slow but continuous release was seen until 96 h following Higuchi release kinetics. DTX-NPs were able to maintain their desired characteristics when studied at accelerated conditions of stability. Conclusions: In-vivo study indicated that the optimized nanoparticles were well retained in lungs and that the drug level could be maintained for a longer duration if given in the form of DTX-NPs by the pulmonary route. Thus, the non-invasive nature and target specificity of DTX-NPs paves the way for its future use as a pulmonary delivery for treating non-small cell lung cancer (NSCLC).


Assuntos
Antineoplásicos/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/administração & dosagem , Antineoplásicos/uso terapêutico , Docetaxel/uso terapêutico , Humanos , Nanopartículas/uso terapêutico , Poloxâmero/administração & dosagem , Poloxâmero/uso terapêutico , Resultado do Tratamento
20.
Urologe A ; 58(9): 1066-1072, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31041460

RESUMO

There is an ongoing change of paradigm in the treatment of metastatic prostate cancer (mPC). Taxan-based chemotherapy demonstrated a prolonged survival of patients in several randomized phase III trials. This is true in the situation of metastatic castration-resistent prostate cancer (mCRPC) as well as in the hormone-naïve stage (metastatic castration-naive PC [mCNPC]). In patients with mCNPC, treatment with docetaxel in combination with androgen deprivation therapy (ADT) prolonged the median total survival time by 15 months in comparison to ADT alone. Comparable results were obtained by the endocrine combination treatment with ADT/abiraterone. With the current data in mind it seems to be useful to discuss the value of early combination therapy with ADT/docetaxel or ADT/abiraterone as well as the impact on further treatment options in the mCRPC setting and to define criteria for treatment decisions in clinical practice.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/terapia , Antagonistas de Androgênios/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Docetaxel/administração & dosagem , Humanos , Masculino , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento
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